Novel amplicons on the short arm of chromosome 7 identified using high resolution array CGH contain over expressed genes in addition to EGFR in glioblastoma multiforme

Amplification of a defined chromosome segment on the short arm of chromosome 7 has frequently been reported in glioblastoma multiforme (GBM), where it is generally assumed that it is the result of over expression of the epidermal growth factor receptor (EGFR) gene that provides the selective pressure to maintain the amplification event. We have used high resolution array comparative genomic hybridization (aCGH) to analyze amplification events on chromosome 7p in GBM, which demonstrates that, in fact, several other regions distinct from EGFR can be amplified. To determine the changes in gene expression levels associated with these amplification events, we used oligonucleotide expression arrays to investigate which of the genes in the amplified regions were also over expressed. These analyses demonstrated that not all genes in the amplicons showed increased expression, and we have defined a series of over expressed genes on 7p that could potentially contribute to the development of the malignant phenotype in these tumors. The global analysis of amplification afforded by aCGH analysis has improved our ability to define numerical chromosome abnormalities in cancer cells and has raised the possibility that genes other than EGFR may be important.